About this Author

College chemistry, 1983

The 2002 Model

After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases.
To contact Derek email him directly: derekb.lowe@gmail.com
Twitter: Dereklowe

May 3, 2012

A Long-Delayed COX2 Issue Gets Settled - For $450 Million?

Posted by Derek

Has the last shot been fired, very quietly, in the COX-2 discovery wars? Here's the background, in which some readers of this site have probably participated at various times. Once it was worked out that the nonsteroidal antiinflammatory drugs (aspirin, ibuprofen et al.) were inhibitors of the enzyme cyclooxygenase, it began to seem likely that there were other forms of the enzyme as well. But for a while, no one could put their hands on one. That changed in the early 1990s, when Harvey Herschman at UCLA reported the mouse COX2 gene. The human analog was discovered right on the heels of that one, with priority usually given to Dan Simmons of BYU, with Donald Young of the University of Rochester there at very nearly the same time.

The Rochester story is one that many readers will be familiar with. The university, famously, obtained a patent for compounds that exerted a therapeutic effect through inhibition of COX-2, without specifying what compounds those might be. They did not, in fact, have any, nor did they give any hints about what they'd look like, and this is what sank them in the end when the university lost its case against Searle (and its patent) for not fulfilling the "written description" requirement.

But there was legal action on the BYU end of things, too. Simmons and the university filed suit several years ago, saying that Simmons had entered into a contract with Monsanto in 1991 to discover COX2 inhibitors. The suit claimed that Monsanto had (wrongly) advised Simmons not to file for a patent on his discoveries, and had also reversed course, terminating the deal to concentrate on the company's internal efforts instead once it had obtained what it needed from the Simmons work.

That takes us to the tangled origin of the COX2 chemical matter. The progenitor compound is generally taken to be DuP-697, which was discovered and investigated before the COX-2 enzyme was even characterized. The compound had a strong antiinflammatory profile which was nonetheless different from the NSAIDS, which led to strong suspicions that it was indeed acting through the putative "other cyclooxygenase". And so it proved, once the enzyme was discovered, and a look at its structure versus the marketed drugs shows that it was a robust series of structures indeed.

One big difference between the BYU case and the Rochester case was the Simmons did indeed have a contract, and it was breach-of-contract that formed the basis for the suit. The legal maneuverings have been going on for several years now. But now Pfizer has issued a press release saying that they have reached "an amicable settlement on confidential terms". The only real detail given is that they're going to establish the Dan Simmons Chair at BYU in recognition of his work.

But there may be more to it than that. Pfizer has also reported taking a $450 million charge against earnings related to this whole matter, which certainly makes one think of Latin sayings, among them post hoc, ergo propter hoc and especially quid pro quo. We may not ever get the full details, since part of the deal would presumably include not releasing them. But it looks like a substantial sum has changed hands.

@1 - I don't think so; there was a previous ~ $1MM that got paid out for lawyers fees a bit ago, and it'd be unusual for a settlement like this to have more than a 50:50 (and personally I'd have guessed closer to 2:1 for Simmons / BYU), despite the abundance of pro hac vice's on the last court filing.

According to BYU's tech transfer page, BYU gives 45% of revenues collected to inventors (which is incredibly generous at large sums, most uni's have a diminishing percentage given). I don't know if this case here, since its not a straightforward license/sale of a patent

The timeline on all this seems wrong. I was at Monsanto in the mid-80s but not in the Healthcare division (later merged with Searle about 1985). There was already work in progress then on COX inhibitors at that time. Although I was not directly involved in the project, there were frequent discussions of the advantages compared to the NSAIDs in internal communications and meetings. I'm not sure exactly what BYU and Rochester brought to the project as there were already compounds in testing.

I worked in Don Young's lab from 1986 until 88 when I moved to Maryland to work on HPV at the former BRL (now Digene-qiagen). Don was a pioneer in the field. I recall trying to purify spots off 2D gels by re-electrophoresis through capillary tubes before CE or protein sequencing was invented. I only recently learned one of those 2300 spots we used to try to analyze that were "induced" by certain mitogens was COX-2. I am always grateful for the experience. Should have stayed on and finished my PhD :-)